Process for making alkyl-1, 1-dimethylindans



rates Jersey No Drawing. Filed Mar. 2, 1960, Ser. No. 12,267 14 Claims.(Cl. 260668) This invention relates to 6-alkyl-l,l-dimethylindans and6-alkyl-1,l,2-trimethylindans and a new method of producing them. Morespecifically it relates to the condensation of monoalkyl-substitutedbenzenes with 2-methyl-1,3- butadiene or 2,3-dimethyl-1,3-b-utadiene inthe presence of acidic condensing agents to produce6-alkyl-1,l-dimethylindans or the corresponding6-alkyl-1,1,2-trimethylindans.

Object of this invention is to produce 6-alkyl-1,1-dimethylindans and6-alkyl-1,1,2-trimethylindans by a simple, convenient and inexpensiveprocess readily adaptable to commercial usage. The advancement of theart is a further object. The disclosure of a hithertofore unknownreaction is a further object.

In the past compounds of the type produced by this invention have beensynthesized by expensive multistep methods usually involving formationof a Grignard reagent followed by condensation to yield a tertiaryalcohol. Cyclodehydration of the tertiary alcohol by the method ofDavidson and Bogert (J. Am. Chem. Soc. 56, 185 (1934)) yields thehydrocarbon 1,1-dimethylindan. Finally, alkylation is effected toproduce an isomeric mixture containing and 6-alkyl-l,l-dimethylindans.For example, this procedure is followed by Beets and coworkers in thesynthesis of an isomeric mixture of tort.- butyl-l,l-dimethylindans(Rec. Trav. Chim. 77, 856 (1958)). A similar approach is outlined in thepatent literature (Beets et al. US. 2,889,367 and German Patent1,059,902). It has recently been shown that the intermediate,l,l-dimethylindan, may be synthesized by cyclization ofB-phenylisovaleric acid with polyphosphoric acid to produce3,3-dimethyl-1-indanone followed by reduction, either catalytically orby the Wolff-Kishner method (Ferrero and Helg, Helv. Chim. Acta XLII,2111 (1959)). While the above-mentioned methods are undoubtedly of greatacademic interest, it is obvious that they are unsuitable for productionon a commercial scale owing to the great number of steps involved andexpensive reactants employed; furthermore, it is obvious that separationof the pure 6-alkyl-l,l-dimethylindan isomer from its mixture would bequite diflioult and expensive to carry out on a technical scale.

Now I have discovered that 6-alkyl-1,l-dimethylindans can be easilysynthesized by a simple one-step reaction using cheap and readilyavailable chemicals, namely, isoprene, acid catalysts, e.g., sulfuricacid, 93%, and the monoalkylbenzenes. By the process of this inventionthere are obtained indans having mainly the 6-alkyl-l,ldimethylindanstructure although in certain cases a minor percentage of isomers,presumably the 4 or 5-alkyl-l,ldimethylindans, are shown to be presentby the vapor phase chromatograms. In the case of the reaction ofisoprene with oumene or with tert.-butylbenzene the resultingfi-isopropylor 6-tert.-butyl-l,l-dimethylindans are obtained in a highdegree of purity as shown by their ECC vapor phase chromatograms andcomparison of their infra-red absorption spectra with that of the pureauthentic hydrocarbons.

The overall reaction may be represented as follows:

fins OH: H o-orrs acid I R1 catalyst R \Rl OH; on,

where R is a lower alkyl and R is hydrogen or methyl.

Advantageously, the reaction is conveniently carried out by the slowaddition of the -diene or a solution of the -diene in an inert solventin the monoalkylbenzene to a cold, rapidly-stirred (-10 to 10 C.)suspension of the monoalkylbenzene in aqueous concentrated sulfuric acid(93%). The reaction temperature is maintained at -10 to 10 C. during theaddition which usually requires from 2 to 3 hrs. depending on theefficiency of the cooling. After addition is completed, the mixture isstirred a short time and quenched, or the acid separated. After beingwashed neutral the solution is vacuum-distilled to yield the indan. Analternate mode of operation is to feed a solution of the -indene and allof the monoalkylbenzene slowly into the cold sulfuric acid.

It is an advantage of this process that it may be operated at lowtemperature under atmospheric pressure. The preferred reactiontemperatures are considerably lower than the boiling point of isopreneand this reduces the hazard of fire and explosion. Furthermore,apparatus suitable for carrying out reactions under atmospheric pressureis considerably cheaper and simpler in construction and design than thatrequired for pressure reactions.

Monoalkylbenzenes which have been successfully condensed are toluene,ethylbenzene, oumene, tert.-butylbenzene, sec.-butylbenzene andtert.-amylbenzene. Technical grades of the -dienes, which arecommercially available, have been found suitable for the process.

While, as aforesaid, aqueous sulfuric acid of about 93% concentrationgives advantageous results, sulfuric acid of other concentrations, aswell as other condensing catalysts may be used in accordance with thepresent invention. Thus, sulfuric acid within the range from about toabout 96% strength has been found to give desirable results. The 93%strength sulfuric acid is preferred because it is commerciallyavailable, gives excellent yields with a minimum of by-products and hasa low freezing point much below the temperature of the reaction.

Other acids which may be used as condensing catalysts herein are thoseacids which are capable of acting as Friedel-Crafts condensingcatalysts. Examples of such acids are phosphoric acid, polyphosphoricacid, boron trifiuoride-Water complex and hydrofluoric acid.

In carrying out the process of this invention the proportions of theingredients may be varied over wide limits. It is preferred to use atleast 1 mol and advantageously 2 to 10 mols of the monoalkylbenzene permol of diolefin in order to minimize side reactions, such aspolymerization of the diolefin. The acid catalysts may be employed inamounts varying from about 5 to about 100%, by weight, based on themonoalkylbenzene employed.

The temperature at which the process of this invention is carried outmay also be varied over wide limits, i.e., from about -30 C. to about150 C. When sulfuric acid is employed, the temperature mayadvantageously be from about 30 C. to about 80 C. In general, the higherthe acid strength, the lower the temperature to be used. Thus, whensulfuric acid of about 75%-80% strength is used, a temperature above 500, preferably about 60 C. to 80 C. is desirable. When sulfuric acid ofabout 80% to 90% concentration is used, a temperature within the rangefrom about C. to about 50 C. is suitable. With sulfuric acid of 90%96%strength, a temperature from about 30 C. to about C., preferably fromabout 10 C. to 10 C., is desirable.

When milder condensing acids, such as phosphoric and polyphosphoricacids, are used, higher reaction temperatures, such as aboi e 105 -150C., are suitable. Anhydrous HP is active at about the same temperaturesas 93% sulfuric acid, namely, to 50 C. The BF -H O catalyst is quiteactive at 25 to C.

The indansforrned by the process of this invention are suitable for useas chemical intermediates and intermediates for odorants, including muskodorants. For example, Beets and co-workers (Rec. Trav. Chim. 77, 856(1958)) have shown that acetylation of compounds having the structure:

CH3 CH where R=tert.-butyl, sec.-butyl, tert.-amyl and isopropyl, givederivatives of musk-like odor. The identity of the correspondinghydrocarbons formed from isoprene in the process of this invention wasproven by the preparation of the acetyl derivatives, which proved to besolids of musk-like odor, having melting points the same as Beetsreported. In addition, it was found that the 4-(and 5-)acetyl-1,1-dimethyl-6-ethylindan, prepared starting with ethylbenzene,exhibited musk-like odor. In order to further prove the structures ofthe indans prepared from isoprene and cumene and tert.-butylbenzenethese hydrocarbons were synthesized by classical procedures from4-isopropylbenzaldehyde and 4-tert.-butylbenzaldehyde respectively bythe method outlined by Beets and co-workers foracetyl-1,1-dimethyl-6-isopropylindan (Rec. Trav. Chim. 77, 864' (1958)).The infra-red absorptioncurves were similar in both cases to thecorresponding indans made by v EXAMPLE I 1 ,1 ,6-Trimethylindan Into arapidly-stirred suspension of 300 g. 93% sulfuric acid and 650 g. oftoluene at --4 C. was slowly added dropwise a solution of 115 g.isoprene (1.69 moles) and 200g. toluene over a 4 hr. period keeping thereaction mixture 4 to +1 C. Stirring at this temperature was containedminutes longer after the feed. The mixture was allowed to settle and thelower sulfuric acid layer separated and discarded (307 g.). Theremaining oil layer was washed successively with water, 5% caustic sodasolution and sodium bicarbonate solution. The excess toluene wasdistilled off and the residual liquid vacuum-distilled to yield as themain fraction 114 g., a

colorless liquid, B.P. 55 C. (1 mm.), n 1.5134, consisting mainly of1,1,6-trimethylindan. Its vapor-phase chromatograrn indicated purity andthe presence of minor amounts of isomers or by-products.

The acetyl derivative was prepared and obtained as a viscous colorlessliquid, B.P. 117 (2 mm.), 21 1.5397, having a rather pleasantacetophenone-type odor.

EXAMPLE II 1 ,1,2,6-Tetramethylindan Into a rapidly-stirred suspensionof toluene (500 g.) in 93% sulfuric acid (150 g.), chilled to 5 C., wasadded dropwise with vigorous agitation a solution of 138 g. 2,3-dimethyl-1,3-butadiene (1.68 moles) in 250 g. toluene over a 3 /2 hourperiod while maintaining the temperature at 6 to 0 C. Stirring wascontinued for 40 minutesafter the feed. After settling and discardingthe sulfuric acid, the oil layer was washed successively with water(2x200 ml.), 5% caustic soda solution ml.) and 5% sodium bicarbonatesolution (200 ml.). After removal of toluene by distillation theresidual liquid was vacuum-distilled yielding as principal product 65 g.1,1,2,

6-trimethylindan, a colorless liquid, B.P. 7779 (3 mm.),

EXAMPLE In 6-Ethyl-l ,1 -Dimethylimlan Into a vigorously agitatedsuspension of 275 g. 93% sul,

The vapor-phase chromatogram indicated a purity of over 90%.

4-(and 5-) acetyl-6-ethyl-1,1-dimethylindan was prepared by thelow-temperature (1 to +4 C.) acetylation of the hydrocarbon using acetylchloride, aluminum chloride and carbon tetrachloride as solvent. Theproduct was a colorless liquid, moderately viscous, B.P. 122-123 (1.5mm.), n 1.5335 having a musk-like odor.

EXAMPLE IV 6-Ethyl-1,LZ-Trimethylindan Into a vigorously agitatedsuspension of 616 g. 93%,, sulfuric acid and 500 g. of ethylbenzene,chilled to 2 C., there was added dropwise over a 2 /2 hour period asolution of 138 g. 2,3-dirnethyl-1,3-butadiene (1.68 moles) and 250 g.ethylbenzene with good agitation and cooling at 5 to 0 C. Stirring inthe cold was continued for 40 minutes longer after the feed. Aftersettling and separating the sulfuric acid the reaction solution waswashedv free of acid and vacuum-distilled over a trace of soda ash.After recovery of excess ethylbenzene there was obtained the desired6-ethyl-1,1,2-trimethylindan as fraction, B.P.. 8787.5 C. (3.5 mm.) 111.5109, amounting to 68 g. The hydrocarbon is a mild-smelling colorlessliquid.

EXAMPLE V 6-l's0pr0pyl-1,I-Dimethylindon Into a rapidly stirred mixtureof 308 g. of 93% sulfuric acid and 684 g. cumene at 5 there was slowlyadded dropwise a solution of g. isoprene in 200 g. cumene at such a ratethat the reaction temperature could be maintained at 5 to 0 throughoutthe feed. Stirring was continued at 0 for 40 minutes after the feed wascomplete. After allowing to settle, the lower sulfuric acid layer wasdiscarded and the remaining oil layer was washed successively withwater, 5% caustic soda solution and 5% bicarbonate of soda solution. Thewashed solution was then subjected to vacuum-distillation, yieldingbesides recovered cumene, the 1,1-dimethyl-6-isopropylindan as acolorless liquid, B.P. 75-77 (3 mm.), 11 1.5084, sp. gr. 25/25=.8986,amounting to 168 g. The vapor-phase chromatogram indicated a purity ofgreater than 95%.

Acetylation at in carbon tetrachloride solution yielded a mixtureprobably consisting of 4- and S-acetyl- 1,1 dimethyl 6 isopropylindan,B.P. 1141l6 C. (1 mm.), n 1.5261, from which a crystalline isomer wasobtained, M.P. 48.549.0 C., having a strong musk-like odor. This isomerwas described as the 4-acetyl derivative by Beets (Rec. Trav. Chim. 77,859 (1958)).

EXAMPLE VI 6-Is0pr0pyl-1 ,1 ,Z-Trimethylindan Into a rapidly stirredmixture of 308 g. of 93% sulfuric acid and 684 g. cumene cooled to therewas slowly added dropwise a solution of 138 g. of 2,3-dimethyl-1,3-butadiene in 144 g. of cumene at such a rate that the reactiontemperature could be maintained at -5 to 0 throughout the feed. Stirringwas continued for 40 min utes after the feed. After allowing to settlein the cold (O5) the lower sulfuric acid layer was discarded and theremaining oil layer was washed successively with water, 5% caustic sodasolution and 5% bicarbonate of soda solution. The resulting washedsolution was then subjected to vacuum-distillation yielding, afterremoval of excess cumene, the desired indan as a colorless fraction,B.P. 92-93 (2 mm.),-n 1.5061, sp. gr. 25/25 .8964, amounting to 123 g.v

4-(and 5-)acetyl-6-isopropyl-1,1,2-trimethylindan. The acetyl derivativewas prepared by feeding the above indan (79.5 g.) into a cold (0 C.)mixture of carbon tetrachloride (300 ml.) and granular aluminum chloride(59.5 g.) and acetyl chloride (40.0 g.) over a 2 /2 hour period. After 2hrs. additional stirring at 1 to 3 the batch was quenched. After workingup in the usual manner, the acetyl derivative was obtained byvacuum-distillation as a pale yellow viscous liquid, B.P. 125 C. (1.2mm.), 11 1.5255, having a sweet somewhat musk-like odor.

EXAMPLE VII 6-Tert.-Butyl-1,1 Dimethylindcm Into a rapidly stirredmixture of 308 g. 93% sulfuric acid and 770 g. tert.-butylbenzene at 5C. was slowly fed a solution of 115 g. isoprene (1.69 moles) in 154 g.tert.-butylbenzene over a 2 hr. period keeping the reaction mixture at 5to 0 C. during the feed. The reaction mixture was stirred for 40 minutesafter the feed was finished. After allowing to settle the lower sulfuricacid layer was separated and discarded. The oil layer was washedsuccessively with Water, 5% caustic soda solution and sodium bicarbonatesolution. The excess tcrt.-butylbenzene was then distilled off (15 mm.)and the residual liquid vacuum-distilled to yield 17 g. of intermediatefraction, B.P. 3579 (2 mm.), and 207 g. of product consisting mainly of6-tert.-butyl-1,1-dimethylindan, B.P. 79-87 (2 mm), 11 1.5045 to 1.5066,a colorless liquid of mild odor. There was obtained 11 g. ofhigher-boiling fraction (B.P. 8792 at 2 mm.) and 34 g. of residue.

The 6-tert.-butyl-1,1-dimethylindan thus obtained was compared with thematerial synthesized by the method of Beets and coworkers, (Rec. Trav.Chim. 77, 865 (1958) (Compound XIla)) by examination of infrared spectraand found to be identical. Vapor-phase chromatogram indicated purityabove 95%.

Acetylation of the indan by the method of part 2 of Example I of US.Patent 2,889,367 gave a solid acetyl derivative having a melting pointof 7777.5 and possessing a strong musk-like odor.

EXAMPLE VIII 6-Tert.-Butyl- 1 ,1 ,Z-Trimetlzylindan Into a cold, stirredmixture of 308 g. of 93% sulfuric 6 acid and 770 g. oftert.-butylbenzene at 5 C. was slowly added dropwise a solution of 138g. 2,3-dimethyl-1,3-butadiene (1.68 moles) and 154 g. tert.-butylbenzeneat such a rate that the reaction mixture could be maintained at 5 to 0C. over the 3 hr. addition time. After the feed was complete, stirringwas continued for 40 minutes longer. After settling, the lower sulfuricacid layer was discarded and the oil layer was washed successively withwater, 5% caustic soda solution and 5% bicarbonate of soda solution; itwas then filtered through Super-Cel and vacuumdistilled over 1 gram ofbicarbonate of soda. After removal of unreacted tert.-butylbenzene (B.P.69-72" C. 25 mm.) there was obtained a forerun (B.P. 2585 C. 1.5 mm.)amounting to 29 g. followed by the desired 1,1,2-trimethyl-6-tert.-buty-lindan, B.P. 88.592 C. (1.5 mm.), 11 1.5055, a 03 0.8970 acolorless liquid amounting to 154 g. The yield was 43.3% of theory.

EXAMPLE IX 6-Sec.-Butyl-1,1-Dimeflzylindan Into a rapidly stirredmixture of 308 g. of 93% sulfuric acid and 500 g. of sec.-butylbenzeneat -4 was slowly fed a solution of 155 g. of isoprene in 200 g.sec.-butylbenzene over a 4 hr. period while the reaction mixture wasstirred and maintained at 4 to 1 C. during the feed. The reactionmixture was stirred in the cold for 40 minutes longer after the feed.After settling, the lower sulfuric acid layer was run oft" anddiscarded. The oil layer was washed successively with-water, 5% causticsoda solution and sodium bicarbonate solution. The excesssec.-butylbenzene was distilled off at 2 mm. (B.P. 35-38") and theresidual liquid vacuum-fractionated to yield 149 g. B.P. 8798 C. (2-3mm. of mercury), n 1.5130 of the 6-sec.-butyl-1,l-dimethylindan.

Acetylation was conducted at lower temperature by the usual technique toyield an acetyl derivative as a pale yellow liquid, B.P. 145147 C. (3.5mm.), 11 1.5244, having a musk-like odor reminiscent of ambrette seedoil.

EXAMPLE X 6-Tert.-Amyl-1 ,1 Dim ethyl indan Into a rapidly stirredmixture of 154 g. of 93% sulfuric acid and 276 g. tert.-amylbenzenecooled to -9 C. was added dropwise a solution of 58 g. isoprene in g.tert. amylbenzene over a 3 hr. period maintaining good cooling (-9 to 0C.) and stirring. The reaction mixture was stirred at 0 C. for 40minutes longer after the feed. The sulfuric acid was settled out andseparated as a lower layer. The remaining oil layer was washedsuccessively with water, 5% caustic soda solution and sodium bicarbonatesolution. Upon vacuum fractionation there was obtained 65 g. of6-tert.-amyl-1,l-dimethylindan a colorless liquid, B.P. 9296 C. (2 mm),11 1.5050, (1.2 0.8958. Analysis by vapor-phase chromatogram indicated apurity of 93%.

4- (and 5-) Acetyl-6-TerL-Amyl-I,1-Dimethylindan Fifty-six and one-halfgrams of the above indan were acetylated at low temperature using 40 g.granular aluminum chloride, 27 g. acetyl chloride and 200 ml. carbontetrachloride as solvent. After working up in the usual manner theacetyl derivative was obtained as a colorless liquid, B.P. 142144.5 C.(3 mm.), n 1.5210, having a musk-like odor. This fraction becamepartially crystal, line on standing. The solid part was separated andpuri? fied by recrystallization from methanol to give colorlesscrystals, MP. 47 50 C., having a musk-like odor.

When the experiments set forth in the foregoing Examples I to X wererepeated, using :10 C. to 10 C. as the temperature range for thereaction, it was found that substantially the same results were obtainedas set forth in the foregoing examples.

The foregoing illustrates the invention, which however is not to belimited thereby but is to be construed as broadly as permissible in viewof the prior art and limited solely by the appended claims.

I claim:

1. The process for preparing alkyl-l,l-dimethylindans, unsubstituted inthe 3-position, which comprises reacting a lower alKyl-substitutedbenzene with a member selected from the group consisting of isoprene and2,3-dimethyi- 1,3-butadiene in the presence of an acid catalyst usefulin bringing about Friedel-Crafts reactions, at a temperature within therange from about 30 C. to about 150 C.

2. The process of claim 1, wherein said member is isoprene.

3. The process of claim 1, wherein said catalyst is aqueous sulfuricacid of about 75 to about 96% concentration and said temperature iswithin the range from about -30 C. to about 80 C.

4. The process of claim 1, wherein the catalyst is sulfuric acid ofabout 93% concentration and the temperature is within the range fromabout l C. to about C.

5. The process for preparing 1,1,6-trimethylindan, which comprisesreacting toluene and isoprene in the presence of sulfuric acid of about93% concentration at a temperature within the range from about 10 C. to10 C.

6. The process for preparing l,1,2,6-tetramethylindan, which comprisesreacting toluene with 2,3-dimethyl 1,3- butadiene in the presence ofsulfuric acid of about 93% concentration at a temperature within therange from about 10 C. to 10 C.

7. The process for preparing 6-ethyl-l,l-dimethylindan, which comprisesreacting ethyl benzene and isoprene in the presence of sulfuric acid ofabout 93% concentration at a temperature within the range from about l0C. to 10 C.

8. The process for preparing 6-ethyl-l,l,2-trirnethylindan, whichcomprises reacting ethylbenzene with 2,3-dimethyl-1,3-butadiene in thepresence of sulfuric acid of about 93% concentration at a temperaturewithin the range from about 10 C. to 10 C.

9. The process for preparing 6-isopropyl-1,l-dimethylindan whichcomprises reacting curnene and isoprene in the presence of sulfuric acidof about 93% concentration at a temperature within the range from aboutl0 C. to 10 C.

10. The process for preparing 6-isopropyl-l,l,2-trimethylindan, whichcomprises reacting cnmene with 2,3- dimethyl-l,3-butadiene in thepresence of sulfuric acid of about 93% concentration at a temperaturewithin the range from about 10 C. to 10 C.

11. The process for preparing 6-tertiary-butyl-1,l-dimethylindan, whichcomprises reacting tertiary-butyl benzene with isoprene in the presenceof sulfuric acid of about 93% concentration at a temperature within therange from about l0 C. to 10 C.

12. The process for preparing 6-tertiary-butyl-l,1,2-trimethylindan,which comprises reacting tertiary-butyl benzene with2,3-dimethyl-1,3-butadiene in the presence of sulfuric acid of about 93%concentration at a temperature within the range from about 10 C. to 10C.

13. The process for preparing d-secondary-butyl-l,l-dimethylindan, whichcomprises reacting secondary-butyl benzene with isoprene in the presenceof sulfuric acid of about 93% concentration at a temperature within therange from about l0 C. to 10 C.

14. The process for preparing 6-tertiary-amyi-l,1-dimethylindan, whichcomprises reacting tertiary-amyl benzene with isoprene in the presenceof sulfuric acid of about 93% concentration at a temperature within therange from about 10 C. to 10 C.

References Cited in the file of this patent UNITED STATES PATENTS1,934,123 Hoffman et al Nov. 7, 1933 2,603,655 Strain July 15, 19522,752,404 Polak June 26, 1956 2,815,381 Carpenter et al. Dec. 3, 1957FOREIGN PATENTS 796,130 Great Britain June 4, 1958 UNITED STATES PATENTOFFICE CERTIFICATE OF CORRECTION ?atent No 3,078,319 February 19, 1963Thomas F., Wood It is hereby certified that error appears in the abovenumbered patent requiring correction and that the said Letters Patentshould read as corrected belo* Col umn 2, line 14, after "solvent"insert or line 24,- Eor "'-1ndene" read "-die'ne" column 6, line 36,"for 'lower"- read low Signed and sealed this 20th day of August 1963.

SEAL) .ttest:

IRNEST W. SWIDER ,ttesting Officer DAVID L. LADD Commissioner of Patents

1. THE PROCESS FOR PREPARING ALKYL-1, 1-DIMENTHYLINDAHS, UNSUBSTITUTEDIN THE 3-POSITION, WHICH COMPRISES REACTING A LOWER ALKYL-SUBSTITUTEDBENZENE WITH A MEMBER SELECTED FROM THE GROUP CONSISTING OF ISOPRENE AND2,3-DIMENTHYL1,3-BUTADIENE IN THE PRESENCE OF AN ACID CATALYST USEFUL INBRINGING ABOUT FRIEDEL-CRAFTS REACTIONS, AT A TEMPERATURE WITHIN THERANGE FROM ABOUT -30* C. TO ABOUT 150* C.